11-68021524-C-G

Position:

• chr11-68021524-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000694.4(ALDH3B1):​c.602C>G​(p.Ala201Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALDH3B1 NM_000694.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.81

Genes affected

ALDH3B1 (HGNC:410): (aldehyde dehydrogenase 3 family member B1) This gene encodes a member of the aldehyde dehydrogenase protein family. Aldehyde dehydrogenases are a family of isozymes that may play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. The encoded protein is able to oxidize long-chain fatty aldehydes in vitro, and may play a role in protection from oxidative stress. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41500944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH3B1	NM_000694.4	c.602C>G	p.Ala201Gly	missense_variant	7/10	ENST00000342456.11	NP_000685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH3B1	ENST00000342456.11	c.602C>G	p.Ala201Gly	missense_variant	7/10	1	NM_000694.4	ENSP00000473990.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2024

The c.602C>G (p.A201G) alteration is located in exon 7 (coding exon 6) of the ALDH3B1 gene. This alteration results from a C to G substitution at nucleotide position 602, causing the alanine (A) at amino acid position 201 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Benign	0.91
DEOGEN2	Uncertain	0.43	T;T;T;.
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	.;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.41	T;T;T;T
PrimateAI	Uncertain	0.54	T
Sift4G	Uncertain	0.035	D;D;D;D
Polyphen		0.057	B;.;B;B
Vest4		0.50
MVP		0.51
GERP RS		3.8
Varity_R		0.20
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-67788993;